Neutrophil-Percentage-to-Albumin Ratio Outperforms High-Sensitivity C-Reactive Protein in Predicting Mortality in Acute Heart Failure: Evidence from a Nationwide Prospective Cohort

Zhanyuan Chen,1,* Yu Wei,1,* Yaoyao Wang,2 Rui Zhu,1 Haoran Ji,1 Yaxin Liu,3 Jianfang Cai41Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, National Center for Cardiovascular Diseases, Beijing, 100037, People’s Republic of China; 2Department of Nephrology, The First Hospital of Tsinghua University, Beijing, 100016, People’s Republic of China; 3Department of Cardiology, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, National Center for Cardiovascular Diseases, Beijing, 100037, People’s Republic of China; 4Department of Nephrology, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, National Center for Cardiovascular Diseases, Beijing, 100037, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jianfang Cai, Department of Nephrology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 167 Beilishi Road, Xicheng District, Beijing, 100037, People’s Republic of China, Tel +86-15801601007, Email caijfbj@fuwaihospital.orgBackground: The neutrophil percentage-to-albumin ratio (NPAR) is a novel inflammatory marker. However, its prognostic role in acute heart failure (AHF) remains unclear.Methods: This post hoc analysis included 4622 patients with AHF from a nationwide prospective cohort in China. The outcomes were all-cause mortality (ACM), cardiovascular mortality (CVM), major adverse cardiovascular events (MACE), and hospitalization for HF (HHF). Multivariable Cox regression was used to assess the associations between NPAR and outcomes. The predictive performance of the models was evaluated using Harrell’s concordance index (C-index), 4-year time-dependent continuous net reclassification improvement (cNRI) and integrated discrimination improvement (IDI).Results: During a median follow-up of 4.61 years, higher NPAR and high-sensitivity C-reactive protein (hs-CRP) showed positive graded associations with mortality. Compared with the lowest NPAR quartile, the hazard ratios (95% CIs) for the second, third, and fourth quartiles were 1.29 (1.12– 1.47), 1.38 (1.20– 1.58), and 1.74 (1.52– 1.99) for ACM, and 1.30 (1.10– 1.53), 1.39 (1.18– 1.63), and 1.72 (1.46– 2.03) for CVM, respectively (all P < 0.001). Similar graded associations were observed for 1-year MACE and HHF. Adding NPAR to the primary multivariable model improved the predictive ability for ACM (C-index from 0.693 to 0.701; cNRI 9.90%; IDI 1.20%) and CVM (C-index from 0.705 to 0.712; cNRI 9.30%; IDI 1.00%) (all P < 0.001). NPAR outperformed hs-CRP for mortality prediction, whereas their combination did not further improve model performance.Conclusion: NPAR was positively associated with risks of ACM, CVM, MACE, and HHF and provided incremental prognostic value for mortality beyond hs-CRP. NPAR may be useful for prognostic risk assessment in AHF and warrants further investigation as a potential alternative to hs-CRP.Keywords: inflammation, biomarker, neutrophil percentage-to-albumin ratio, high-sensitivity C-reactive protein, acute heart failure, prognosis